1. Field of the Invention
The present invention relates to a process for the preparation of 1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline of the formula ##STR2## in optically active form by asymmetric hydrogenation.
It further relates to a novel salt of 1-(p-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline and a process for its preparation.
It also relates to a novel chiral diphosphine having a ferrocene structure and to its use for the preparation of catalysts for asymmetric hydrogenation, to the iridium-phosphine complexes obtainable from the diphosphine and also to a novel chiral amino-phosphine having a ferrocene structure as intermediate in the synthesis of the diphosphine.
2. Background Art
1-(p-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (I) is an intermediate in the synthesis of the antitussive dextromethorphan and the analgesic levorphanol. The targeted preparation of the effective enantiomer of dextromethorphan requires I in the (S)-(-)-configuration, and the synthesis of levorphanol requires I in the (R)-(+)-configuration. A classical process for obtaining these stereoisomers is racemate resolution, which, in this case, is also possible without the use of optically active ancillary reagents (DE-A 34 36 179). The main disadvantage of almost all racemate resolutions is that at least half of the substance used has to be disposed of as waste in the form of the "undesired" enantiomer unless, exceptionally, it too is required in comparable quantities. In the present case, racemization is also possible, meaning that the undesired enantiomer can be recycled as racemate and there are in theory no losses (O. Schnider et al., Helv. Chim. Acta 1954, 37, 710; A. Brossi, O. Schnider, Helv. Chim. Acta 1956, 39, 1376; HU 170 924). This method is, however, rather involved.
A significantly better strategy is the targeted synthesis through a stereoselective reaction, starting from a prochiral precursor. It is known that N-acyl-1-benzylidene-1,2,3,4,5,6,7,8-octahydroisoquinolines can be stereoselectively ("asymmetrically") hydrogenated at the exocyclic double bond using chiral ruthenium-phosphine complexes (JP-A 05/092 958). This process does, however, have the disadvantage that an N-acylated product is obtained whose acyl group has to be cleaved off again in a further synthesis step. Furthermore, the benzylidene compounds are for their part formed as E/Z-isomer mixtures, of which in each case only the Z-isomer can be used for the stereoselective hydrogenation.